title: CD28 can promote T cell survival through a phosphatidylinositol 3-kinase-independent mechanism.
abstract: Phosphatidylinositol 3(PI3)-kinase is implicated in various biological responses, including protection from apoptosis, although its role in antigen-induced T cell death and the molecular effectors it triggers remains ill-defined. Here, we investigated the role of PI3-kinase activity in the prevention of T cell receptor/CD3-induced cell death by CD28. PI3-kinase inhibitors blocked the up-regulation of Bcl-X(L) by CD28, without impairing the prevention of T cell receptor/CD3-triggered apoptosis by CD28, hence showing the existence of a cell-survival pathway independent of PI3-kinase activity and up-regulation of Bcl-X(L). Instead, we show that up-regulation of FasL which is instrumental in CD3-induced apoptosis was prevented upon CD28 co-stimulation. These results indicate that PI3-kinase couples CD28 to Bcl-X(L) up-regulation and provide a molecular basis for the role of CD28 in cell survival through a PI3-kinase-independent mechanism including FasL down-regulation.
authors.affiliation: U119 INSERM, Institut de Cancérologie et d'Immunologie de Marseille, Université de Méditerrannée, France. collette@marseille.inserm.fr
authors.forename: Y
authors.initials: Y
authors.lastname: Collette
authors.forename: D
authors.initials: D
authors.lastname: Razanajaona
authors.forename: M
authors.initials: M
authors.lastname: Ghiotto
authors.forename: D
authors.initials: D
authors.lastname: Olive
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D006825:Hybridomas / Q000276:immunology*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D018106:CD28 Antigens; D019869:Phosphatidylinositol 3-Kinases